There has been considerable research effort in recent years toward the development of HLE (or HNE) inhibitors because it appears that HLE may be responsible for a variety of human diseases. Tests have shown that there is an apparent association between HLE and emphysema. See, for example, Sandbero et al., The New England Journal of Medicine, 304:566 (1981). Other diseases and medical problems, such as arthritis and related inflammatory conditions, dermatitis and ischemia/reperfusion injury have also been associated with HLE. See, Dinerman et al., JACC, Vol. 15, No. 7, June 1990: 1559-63. Accordingly, there is a need for compounds which are effective inhibitors of HLE or HNE.
Typical prior efforts to deal with elastase inhibition are disclosed in the patent literature, for instance, U.S. Pat. Nos. 4,683,241 and 4,801,610.